On May 19, 2021 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported preliminary safety and anti-tumor activity data from the Company’s ongoing Phase 1 clinical trial of MGC018 (Press release, MacroGenics, MAY 19, 2021, View Source [SID1234580280]). This investigational antibody-drug conjugate (ADC) was designed to deliver a DNA alkylating duocarmycin payload to both dividing and non-dividing cells in a B7-H3-dependent manner. The dataset will be presented in a poster titled "Phase 1 Dose Escalation Study of MGC018, an anti-B7-H3 Antibody-Drug Conjugate (ADC), In Patients with Advanced Solid Tumors" (Abstract #2631) at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4-8, 2021.

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Dose Escalation Results Update

The ASCO (Free ASCO Whitepaper) abstract included data as of January 21, 2021; updated data as of a May 3, 2021 cut-off are included below and will be presented at ASCO (Free ASCO Whitepaper).

A total of 29 patients with advanced solid tumors were enrolled in five dose escalation cohorts with MGC018 at 0.5 to 4.0 mg/kg, administered intravenously every three weeks. This included six patients at the 4.0 mg/kg cohort enrolled subsequent to the 2020 ASCO (Free ASCO Whitepaper) poster presentation. A recommended Phase 2 dose (RP2D) was defined as 3.0 mg/kg every three weeks.

mCRPC. Preliminary evidence of anti-tumor activity by MGC018 has been observed, most notably in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Reductions in prostate-specific antigen (PSA) levels of ≥ 50% were observed in five of nine mCRPC patients treated in dose escalation, including one with substantial regression of bone disease. Of the nine patients with mCRPC, eight were evaluated for tumor response, all of whom demonstrated a best response of stable disease. Two of these eight patients had measurable disease; both had reductions in target lesions, including a 29% reduction in one patient. The nine mCRPC patients treated in dose escalation received a median of four therapies prior to MGC018, including taxane chemotherapy (eight patients) and next generation hormonal agents (all patients had previously received abiraterone, enzalutamide or both). All nine mCRPC patients in dose escalation are off therapy. Of the five patients who had ≥ 50% PSA reduction, one withdrew consent (without disease progression) at 4 months, one had new bone lesions at 6 months, one initiated subsequent therapy at 6 months, and two had no progression at 7 months.

Melanoma. During dose escalation, three melanoma patients were administered MGC018 at 4.0 mg/kg (the highest dose administered). All had previously received three different checkpoint inhibitor agents. The best responses in target lesion sum reductions for these patients after being treated with MGC018 were 24%, 28% and 36% (confirmed partial response), with this last patient remaining on MGC018 therapy for more than 6 months as of the data cut-off. Based on these data, MacroGenics recently initiated a melanoma expansion cohort (N=approximately 20).

Safety. Adverse events for the dose escalation cohorts of 0.5 mg/kg to 4.0 mg/kg as of the May 3, 2021 data cut-off were generally consistent with those previously reported at ASCO (Free ASCO Whitepaper) 2020. MGC018-related toxicities included hematologic and skin toxicities that have been clinically manageable. In dose escalation overall, at least one treatment-related adverse event was experienced by 27 of 29 patients (93%). At 4.0 mg/kg, one patient developed a dose-limiting toxicity manifested by Grade 3 fatigue that lasted for more than 72 hours and as previously reported, a Grade 4 neutropenia occurred in a patient in the 2.0 mg/kg cohort.

Preliminary Results for mCRPC Cohort Expansion

As of the May 3, 2021 data cut-off, 28 of the 40 patients in the mCRPC cohort expansion had been enrolled, with disease classification available for 20 of these patients: seven had bone only, nine had mixed soft tissue and bone, and four had soft tissue only. Of the 28 mCRPC patients in cohort expansion, 22 had received at least one dose of MGC018 and had a post-baseline PSA. Eleven of these 22 patients (50%) had a PSA reduction of 50% or greater. All but three of these 22 patients were still on therapy as of the data cut-off. Of 13 patients who had measurable disease, six were not yet evaluable and seven had their first 9-week imaging, of which four had reductions in target lesion sums of 13%, 21%, 27% and 35% (unconfirmed partial response). Twelve of these 13 patients were still ongoing on MGC018.

"We continue to be very encouraged by evolving data from our ongoing Phase 1 study of MGC018. To date, we have observed preliminary signals of anti-tumor effects, including PSA reductions of 50% or more in 16 of 31 (52%) patients with late-stage castration-resistant prostate cancer across dose escalation and dose expansion," said Scott Koenig, M.D., Ph.D., President and CEO. "We are very pleased to report decreases in target lesion sums, including an unconfirmed partial response, in mCRPC patients with measurable disease. Finally, we are encouraged to see anti-tumor activity, including a confirmed partial response, in post-checkpoint melanoma patients who have received MGC018. We look forward to sharing the full data at ASCO (Free ASCO Whitepaper) and providing further updates on our ongoing dose expansion cohorts, including patients with mCRPC, non-small cell lung cancer, triple negative breast cancer, melanoma and squamous cell carcinoma of the head and neck, at subsequent scientific conferences."

Conference Call

MacroGenics’ management will host a conference call and webcast with external guest presenters to discuss the preliminary MGC018 results on Friday, June 4, 2021 at 4:30 P.M. ET. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) ten minutes prior to the start of the call and provide the Conference ID: 1583522. The listen-only audio and slide webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source." target="_blank" title="View Source." rel="nofollow">View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days.

ASCO Presentation

The abstract for MacroGenics’ MGC018 poster presentation was submitted to ASCO (Free ASCO Whitepaper) in February 2021 and is available on the ASCO (Free ASCO Whitepaper) website at View Source The poster will be available for on-demand viewing on the ASCO (Free ASCO Whitepaper) website and on the Events & Presentations page on MacroGenics’ website at View Source on or around June 4, 2021.

About MGC018

MGC018 is an ADC comprised of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody conjugated via a cleavable linker to the prodrug seco-DUocarmycin hydroxyBenzamide Azaindole (DUBA; licensed from Byondis, B.V.), with an average drug-to-antibody ratio (DAR) of ~2.7. DUBA is an alkylating agent that can damage DNA in both dividing and non-dividing cells, causing cell death. B7-H3 is a molecule highly expressed on many solid tumors and associated with a poor clinical outcome. MGC018 is being evaluated in a Phase 1 study (NCT03729596). MacroGenics retains worldwide rights to MGC018.

On May 19, 2021 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported that the Company’s management team will participate in a fireside chat at the Jefferies Healthcare Conference being held from June 1-4, 2021 (Press release, Humanigen, MAY 19, 2021, View Source [SID1234580296]).

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Management will discuss its lead product, lenzilumab, which recently completed a Phase 3 clinical trial of in patients hospitalized with COVID-19, including the publication of the results of the trial and the status of the Company’s submission for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration, in addition to providing an update on the Company’s commercial preparation efforts for lenzilumab, and an overview of the Company’s other development programs.

Details for the upcoming webcast is below:

Jefferies Healthcare Conference

Live Fireside Chat
Date: Wednesday, June 2, 2021
Time: 4:00 PM ET
Link: View Source

On May 19, 2021 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported a trials in progress poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually from June 4-8, 2021 (Press release, Scholar Rock, MAY 19, 2021, View Source [SID1234580312]).

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The DRAGON Phase 1 proof-of-concept trial (NCT04291079) is evaluating SRK-181, a selective inhibitor of TGFβ1 activation, in patients with locally advanced or metastatic solid tumors that have shown primary resistance to checkpoint inhibitor therapies. Dose escalation is progressing in Part A of the trial and the Company expects to advance to the Part B dose expansion portion of the trial in mid-2021.

The trials in progress e-poster will provide an overview of the design of the DRAGON Phase 1 trial and highlight the biomarker analysis being implemented to support the trial. Details of the poster presentation are as follows:

Session: Developmental Therapeutics–Molecularly Targeted Agents and Tumor Biology
Title: "First-in-Human Phase 1 Trial (DRAGON) of SRK-181: A Potential First-in-Class Selective Latent TGFβ1 Inhibitor, Alone or in Combination with Anti-PD-(L)1 Treatment in Patients with Advanced Solid Tumors" (TPS3146)
Date and Time: Friday, June 4, 11:00 AM – 2:00 PM EDT; Poster sessions available on demand in meeting library beginning 9:00 AM EDT on June 4, 2021.
About SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity (1). Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The efficacy and safety of SRK-181 have not been established. SRK-181 has not been approved for any use by the FDA nor any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020

On May 19, 2021 Thermo Fisher Scientific Inc. (NYSE:TMO), the world leader in serving science, and the University of California, San Francisco (UCSF) reported they have formed a strategic alliance to accelerate the development and manufacturing of cell-based therapies (Press release, Thermo Fisher Scientific, MAY 19, 2021, View Source [SID1234580328]).

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Under the agreement, Thermo Fisher will build and operate a 44,000-square-foot, state-of-the-art cell therapy development, manufacturing and collaboration center in leased space on UCSF’s Mission Bay campus, which includes biomedical research facilities and hospitals. The site will offer clinical and commercial cGMP cell therapy manufacturing services, along with associated technology development support, to UCSF and other partners.

Expected to open in 2022, the facility will also serve as a central location where customers and UCSF researchers will have access to Thermo Fisher’s broad portfolio of Cell Therapy Systems (CTS) reagents, consumables, and fit-for-purpose instrumentation and compliant software. The CTS product portfolio is designed to work together, and seamlessly transition from research to clinical manufacturing to address cell therapy production workflow challenges.

"We are bringing together UCSF’s leadership in the newest forms of cellular immunotherapy and Thermo Fisher’s extensive capabilities in cell therapy instrumentation, manufacturing and distribution," said Mark Stevenson, executive vice president and chief operating officer of Thermo Fisher Scientific. "This powerful combination will provide customers – from emerging biotechs to large pharma companies – with integrated, end-to-end solutions to reduce costs and accelerate adoption of cell therapies, ultimately improving patient access to these transformative treatments."

Sam Hawgood, MBBS, chancellor of UCSF, said, "We expect breakthrough treatments for many different diseases and conditions to come from cell therapies. Establishing cell therapy manufacturing in such close proximity to our scientists, clinicians and patients will enable UCSF to catalyze innovation in living therapeutics and use the resulting discoveries to benefit our patients."

On May 19, 2021 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer reported that it has entered into an exclusive distribution agreement with Adium Pharma S.A. ("Adium") to be the exclusive distributor in Latin America of the Company’s antibodies, DANYELZA (naxitamab-gqgk) for the treatment of patients with relapsed/refractory high-risk neuroblastoma and omburtamab, if approved, for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, MAY 19, 2021, View Source [SID1234580428]).

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DANYELZA (naxitamab-gqgk) 40mg/10mL was approved by the U.S. Food and Drug Administration ("FDA") on November 25, 2020 and is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.

Omburtamab is an investigational, monoclonal antibody that targets B7-H3 and is radiolabeled before intraventricular administration. B7-H3 is an immune checkpoint molecule that is widely expressed in tumor cells of several cancer types. In April 2021, the Company submitted a Marketing Authorization Application ("MAA") to the European Medicines Agency for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma. The Company aims to resubmit its Biologics License Application ("BLA") to the FDA for omburtamab by the end of the second quarter or in the third quarter 2021.

The distribution agreement includes the territories of Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay, and certain Caribbean islands. Under the terms of the agreement, Adium will employ its sales and marketing expertise to distribute DANYELZA and omburtamab, if approved, in the territory. In addition, Adium will submit registration files on behalf of the Company in certain parts of the territory. All other unpartnered geographies worldwide remain with the Company. Financial details were not disclosed.

"We are very pleased to enter this distribution agreement with Adium, a company with a commercial presence in 18 countries and a sustained oncology and rare disease business. We hope to leverage Adium’s footprint in Latin America to make DANYELZA and omburtamab, if approved, available to children with unmet medical needs," said Thomas Gad, founder, Chairman and President at Y-mAbs.

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed DANYELZA and omburtamab, which are exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compounds and in Y-mAbs.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information for complete Boxed Warning and other important safety information.